Rationale for early treatment initiation of AD during
infancy
AD is not a stand-alone disorder, but is associated with a variety of
comorbidities, including progression of atopic manifestations, known as
the atopic march. Although results on the existence of a sequential
atopic march have been inconsistent, a growing body of evidence supports
that children with AD are at high risk of developing various atopic
comorbidities including food allergy, asthma, and allergic rhinitis
(24-31). The most apparent
association is found between AD and sensitization to food allergens (24,
27, 28, 31). The mechanism behind the increased susceptibility to food
allergy in patients with AD remains to be deciphered and is
multifactorial, such as the pathogenesis of AD itself (28, 31, 32).
Regardless of the mechanism, earlier onset and more severe disease are
important risk factors for the development of usually multiple food
allergies, arguing for preventative treatment strategies of AD during
infancy (27, 33, 34). To address this hypothesis, a recent multicenter,
randomized controlled trial (RCT), including 1,394 newborns, assessed
the impact of daily emollient use during the first year of life to
prevent AD as well as food allergy and other atopic comorbidities (35).
Unlike other reports, emollients were not able to prevent AD, indicating
that more effective treatment options may be needed to restore the skin
barrier in infants who are at high risk to develop AD and subsequent
atopic comorbidities (35).
The classical course of the atopic march, which progresses from AD to
food allergy, allergic rhinitis, and ultimately asthma, has been
challenged over the years. However, there is an undoubtable association
between these atopic comorbidities, as already has been discussed for AD
and food allergy. Although not every child with AD will be sensitized to
inhalant allergens, several birth cohort studies have demonstrated that
onset of AD during infancy, AD severity, and parental atopy are strong
predictors to develop allergic rhinitis and asthma later in life (12,
25, 26, 36). The German Multicenter Allergy Study (MAS) is until now the
longest birth cohort study, which followed up patients until the age of
20 years (26, 36). The MAS demonstrated that AD, asthma, and allergic
rhinitis particularly coexist as a multimorbidity in patients who have
parents with allergies, implying the importance of yet to be fully
determined genetic factors (26, 37). More longitudinal studies are still
warranted to understand if
treatment at first signs and
symptoms during infancy may prevent the allergic multimorbidity,
especially in those who are at risk to develop atopy.
Additionally, AD was found to be associated with comorbidities beyond
the atopic march, including cardiovascular and neuropsychiatric
disorders (38-40). The latter comorbidity is mostly driven by the impact
of AD on the whole family, particularly so on the QoL of young children
and their caregivers (2, 38, 41). Itching and scratching are the most
distressing early symptoms of the disease, which can lead to
sleeplessness, psychological disorders, social isolation, and overall
poor QoL of patients and their families (3, 42). Similar to atopic
comorbidities, QoL decreases when the severity of AD increases,
emphasizing the need for treatments that rapidly and sustainably relief
pruritus (2).
There is also a considerable economic impact of AD on patients,
patients’ families, and payers. Direct costs of AD are mostly related to
prescriptions, physician visits, hospital costs, and pharmacy costs (2).
These direct costs were calculated to be as high as \euro927 per
patient per year by a recent cross-sectional study performed in nine
European countries, and pose a significant economic burden to the
patient that is more pronounced compared with other chronic diseases,
such as psoriasis and rheumatoid arthritis (43). Furthermore, AD is
associated with a variety of indirect costs due to decreased
productivity and work absenteeism, which are a related to the social and
psychological burden of the disease (2, 44). Paradoxically, the
prevalence of AD was reported to correlate with the socioeconomic
status, whereas patients with severe AD were found to have less
educational attainment resulting in a lower annual income (44, 45).
Consequently, improved care for AD would allow substantial savings on
the short- and long-term for both patients and the society. Therefore,
early treatment of AD is not only essential in treating the skin disease
itself to prevent worsening, but also to prevent the development of
atopic comorbidities and most importantly decrease the significant
burden of AD on the entire family and the society as early as possible.